Positron Emission Tomography
Positron emission tomography (PET) is an imaging method for obtaining quantitative molecular and biochemical information of physiological processes in the body. The most common PET radiotracer in use today is [18F]-fluorodeoxyglucose ([18F]-FDG), a radiolabeled glucose molecule. PET imaging with [18F]-FDG allows to visualize glucose metabolism and has a broad range of clinical indications. Other PET radiotracers are about to enter the clinical use. Among positron emitters, 18F is the most widely used today in the clinical environment.
Decomposition of Radiochemicals—Radiolysis
Radiotracers are obtained after single or multiple step organic synthesis, among which the fluorination with 18F-fluorides. radiosynthetic intermediates are generally involved in such radiosyntheses. These radiosynthetic intermediates can be exposed to high levels of radioactivity and high dose rates which results in some decomposition processes commonly named radiolysis. These side reactions can consume those radiosynthetic intermediates or react with the 18F-fluorides and are detrimental to having high radiochemical yields.
The modes by which radiosynthetic intermediates decompose and their corresponding methods of control were classified in 1960 (Bayly, R. J. and Weigel, H., Self-decomposition of compounds labeled with radioactive isotopes. Nature, 188, 384-387 (1960).) (see Table I below).
TABLE IMode ofdecompositionCauseMethod of ControlPrimaryNatural isotopic decayNone for a given specific(Internal)activityPrimaryDirect interaction ofDilution of the labelled(External)radioactive emissionmolecules(alpha, beta or gamma)with molecules of thecompoundSecondaryInteraction of excitedDilution of labelledspecies with molecules ofmolecules; cooling to lowthe compoundtemperatures; free radicalscavengingChemical andThermodynamic instabilityCooling to lowmicrobiologicalof compound and poortemperatures; removal ofchoice of environmentharmful agents
The compound itself and/or its immediate surroundings will absorb the energy from the radiation. This energy excites the molecules, which can break up or react with other species or compounds. The excited molecular fragments may also react with other labeled compounds producing impurities. Energy absorbed by the immediate surroundings (mainly the solvent) can also produce reactive species, often free radicals, which can subsequently cause destruction of the molecules of radiolabeled compound. Whilst this is occurring, chemical decomposition often takes place as well, as these reactions occur in solution where chemical stability is known to be far more limited.
Secondary Decomposition
This is commonly the greatest path for the decomposition of radiochemicals, and it arises from the interaction of, for example, free radicals created by the radiation energy, with surrounding molecules including the radiolabeled molecules. It is by far the most difficult mode of decomposition to control and it is easily influenced by tiny changes to the environmental conditions. The low chemical content of radiolabeled compounds, particularly at high specific activity, amplifies the problems.
Secondary Decomposition in Water Solutions
The action of ionizing radiation on water is well documented (Thomas, J. K., Elementary processes and reactions in the radiolysis of water. Advances in Radiation Chemistry, 1, 103-198 (1969)). Ionization is known to occur along paths of the beta particles in discrete compartments known as “spurs” (Collison, E. and Swallow, A. J., The action of ionizing radiations on organic compounds. Quarterly Reviews of the Chemical Society, 9, 311-327 (1955)). The most damaging of the reactive species believed to be formed is thought to be the hydroxyl radical (Evans, E. A., Tritium and its Compounds. 2nd edition, Butterworths, London, pp. 642-782 (1974)). This was supported by the hydroxylation reaction of carbon-14 or tritium-labeled phenylalanine, to produce tyrosine and dihydroxyphenylalanine (Waldeck, B., [3H]Dopa in [3H]tyrosine with high specific activity. Journal of Pharmacy and Pharmacology, 23, 64-65 (1971)). In order to lower the decomposition, it is necessary to avoid or lessen the interactions between the damaging radicals and the surrounding molecules including the radiolabeled molecules. This can be achieved by lowering the temperature, diluting the radioactive concentration, and by adding radical scavengers. Ethanol is a common radical scavenger (typically as a 2% solution in water).
Secondary Decomposition in Organic Solvents
The detailed mechanism of decomposition of radiochemicals in organic solvents is not well known, and is expected to be complex. The effect of radiation energy on organic solvents is expected to be very different than that of aqueous media and would produce different forms of reactive species. The chemical purity of the solvent is for sure a critical parameter and well purified or very high quality purchased solvents ought to be used. The presence of peroxide in the solution may cause total destruction of the surrounding molecules including the radiolabeled molecules.
[18F]-Radiolabeled Aromatic Amino Acid
Radiolabeled aromatic amino acid derivatives, such as 18F-FDOPA, 18F-FTYR, 18F-FmTYR, etc. are often used to monitor the metabolism in the dopaminergic system. These radiotracers can be indicated to monitor Parkinson disease (PD), Alzheimer disease (AD) and some neurodegenerative diseases. These radiotracers have also shown interest in medical imaging of neuroendocrine tumors (NET).
Radiolabeled aromatic amino acid derivatives can be synthesized following different methods or paths such as for example:

However, most of these syntheses show drops in the radiochemical yields at high level of radioactivity due to the instability of the benzylic and/or phenolic radiosynthetic intermediates.